Vizipak

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT VIZIPAQUE™ (VISIPAQUE™)

Composition:

Active substance: ioxaglate;

1 ml of solution contains: ioxaglate 550 mg, equivalent to 270 mg iodine/ml, or ioxaglate 652 mg, equivalent to 320 mg iodine/ml;

Excipients: trometamol; sodium chloride; calcium chloride dihydrate; calcium disodium edetate; hydrochloric acid 5 M solution to adjust pH to 6.8–7.6; water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical properties: clear, colorless to slightly yellowish solution, practically free from particles.

Pure aqueous solution of ioxaglate at all clinically used concentrations has lower osmolality than whole blood and non-ionic monomeric contrast agents at the same concentrations. VIZIPAQUE is isotonic with normal body fluids due to the addition of electrolytes.

Values of osmolality and viscosity of the product:

Concentration	Osmolality* mOsm/kg H2O at 37 ºC	Viscosity (mPa·s) 20 ºC	Viscosity (mPa·s) 37 ºC
270 mg iodine/mL 320 mg iodine/mL	290 290	11.3 25.4	5.8 11.4

* Method: vapor phase osmometry.

270 mg iodine/ml: 1 ml of the preparation contains 0.76 mg (0.03 mmol) of sodium. This should be taken into account for patients on a controlled sodium diet.

320 mg iodine/ml: 1 ml of the preparation contains 0.45 mg (0.02 mmol) of sodium. This should be taken into account for patients on a controlled sodium diet (see section "Special precautions").

Pharmacotherapeutic group.

Iodine-containing X-ray contrast agents. Water-soluble, low-osmolar, non-ionic X-ray contrast agents. ATC code V08AB09.

Pharmacological Properties.

Pharmacodynamics.

Iodixanol is a non-ionic, dimeric, hexaiodinated, water-soluble X-ray contrast agent.

After injection, the organically bound iodine present in the vessels and tissues absorbs radiation.

In studies conducted on healthy volunteers, intravenous administration of iodixanol did not result in significant alterations in most hemodynamic, clinical-biochemical, or coagulation parameters. Changes in certain laboratory values were minor and are not considered clinically significant.

In certain patient groups, the agent Visipaque has only a minimal effect on renal function. Administration of Visipaque in 3% of 64 diabetic patients with serum creatinine levels of 1.3–3.5 mg/dL was associated with an increase in creatinine levels by ≥ 0.5 mg/dL, but no patient showed an increase by ≥ 1 mg/dL. When Visipaque was administered, enzyme secretion (alkaline phosphatase and N-acetyl-ß-glucosaminidase) in the proximal renal tubules was lower than after administration of non-ionic monomeric contrast agents and similar to that observed after administration of ionic dimeric contrast agents.

The agent Visipaque does not affect renal function.

Cardiovascular parameters such as left ventricular end-diastolic pressure, left ventricular systolic pressure, heart rate, QT interval, and femoral artery flow velocity were less altered after administration of Visipaque compared to other contrast agents.

Pharmacokinetics.

Iodixanol is rapidly distributed in the body. The distribution half-life averages approximately 21 minutes. The volume of distribution corresponds to the volume of extracellular fluid (0.26 L/kg body weight), indicating that iodixanol distributes only into the extracellular fluid. No metabolites have been identified. Plasma protein binding is less than 2%.

The elimination half-life of the drug is approximately 2 hours. Iodixanol is primarily excreted by the kidneys via glomerular filtration. In patients with normal renal function, about 80% of the administered dose is excreted in urine within 4 hours after intravenous injection, and about 97% within 24 hours. Approximately 1.2% of the administered dose is excreted in feces within 72 hours. Maximum urinary concentration of iodixanol is reached 1 hour after injection.

Within the recommended dose range, pharmacokinetics are not dose-dependent. Pharmacokinetic studies of the agent administered into body cavities have not been conducted.

Clinical characteristics.

Indications.

Visipaque is intended for diagnostic use only.

The contrast agent is administered to adult patients for performing cardioangiography, cerebral angiography, peripheral angiography, abdominal angiography, including intra-arterial digital subtraction angiography (DSA), urography, phlebography, contrast enhancement in computed tomography (CT), and gastrointestinal tract examinations.

Lumbar, thoracic, and cervical myelography.

Arthrography, hysterosalpingography (HSG).

The agent is administered to children for cardioangiography, urography, contrast enhancement in computed tomography (CT), and gastrointestinal tract examinations.

Contraindications.

Hypersensitivity to components of Visipaque.

Manifest thyrotoxicosis.

Special safety precautions.

Vials are intended for single use only. Any unused portion of the agent must be discarded.

As with all parenteral preparations, Visipaque should be inspected visually for the presence of insoluble particles, discoloration, or packaging defects prior to administration.

The agent should be drawn into a syringe immediately before use. The contrast agent should be warmed to body temperature prior to administration.

Additional instructions for auto-injector/pump. The 500 ml vial of contrast medium should be used only with auto-injectors/pumps designed for this volume. The vial should be punctured only once.

The catheter connecting the auto-injector/pump to the patient must be replaced after each use. Any unused contrast medium remaining in the vial and in all connecting tubing must be discarded at the end of the working day. For convenience, smaller volume vials may be used. The manufacturer's instructions for the auto-injector/pump must be followed.

Any unused medication or waste material must be disposed of in accordance with local regulations.

Interaction with other medicinal products and other forms of interaction.

Diagnosis of thyroid disorders using any iodine-containing contrast agents may be complicated by reduced iodine-binding capacity of thyroid tissue for up to several weeks, thereby affecting tests measuring iodine uptake (using radioactive iodine).

High concentrations of contrast agents in blood plasma and urine may interfere with laboratory tests measuring bilirubin, protein, or inorganic compounds (e.g., iron, copper, calcium, and phosphates). Such tests should not be performed on the day of the procedure.

The use of iodine-containing contrast agents in diabetic patients receiving metformin may lead to reversible renal impairment and the development of lactic acidosis (see section "Special precautions for use").

Patients who have received interleukin-2 less than two weeks prior to administration of an iodine-containing contrast agent are prone to delayed adverse reactions (flu-like symptoms or skin reactions).

Evidence indicates that the use of β-blockers is a risk factor for the development of anaphylactoid reactions to radiographic contrast agents (severe arterial hypotension has been observed with radiographic contrast agents in patients taking β-blockers).

Patients with asthma are at higher risk when receiving concomitant beta-blocker therapy (see section "Special precautions for use").

Special precautions for use.

General special precautions for non-ionic contrast media.

Hypersensitivity. A history of allergy, asthma, or adverse reactions to iodine-containing contrast agents requires heightened vigilance. In such cases, premedication with corticosteroids and H1- and H2-histamine receptor antagonists should be considered.

The risk of severe adverse reactions to Visipaque is very low. However, iodine-containing contrast agents may cause anaphylactoid reactions or other manifestations of hypersensitivity.

The possibility of developing serious, life-threatening, or fatal anaphylactic/anaphylactoid reactions should always be considered. Most serious adverse reactions occur within the first 30 minutes after administration. Delayed hypersensitivity reactions (occurring 1 hour or more after administration) are possible. Therefore, appropriate emergency treatment procedures, medications, and equipment should be readily available in case of severe adverse reactions. It is recommended to always use a permanent cannula or catheter during radiological contrast procedures to facilitate rapid intravenous administration of medications if needed.

The use of β-blocking agents reduces the threshold and increases the severity of contrast reactions, and also reduces sensitivity to adrenaline treatment of anaphylactoid reactions.
Patients with asthma have an increased risk when receiving concomitant β-blocker therapy (see section "Interaction with other medicinal products and other forms of interaction").

After administration of Visipaque, patients should be observed for at least 30 minutes.

Coagulopathy. Compared to ionic agents, non-ionic iodine-containing contrast agents have less effect in vitro on the blood coagulation system. Clotting of blood has been reported when blood came into contact with syringes containing contrast agents, including non-ionic ones. Data suggest that using plastic syringes instead of glass ones may reduce, but not eliminate, the likelihood of in vitro blood clotting.

During angiographic procedures using either ionic or non-ionic contrast agents, serious, rarely fatal, thromboembolic complications have been reported, leading to myocardial infarction and stroke. Therefore, careful intravascular administration, especially during angiographic procedures, is essential to minimize the risk of thromboembolic complications.

Numerous factors may contribute to the development of thromboembolic complications, including duration of the procedure, material of the catheter and syringe, underlying disease status, and concomitant medication use. For these reasons, strict adherence to angiographic techniques is required, including careful catheter and tubing manipulation, use of multi-component systems and/or three-way stopcocks, frequent flushing of catheters with heparinized sodium chloride solution, and minimizing procedure duration to reduce the risk of intervention-related thrombosis and embolism.

Modern life-support equipment should be immediately available.

Caution is advised when examining patients with homocystinuria (due to the risk of thromboembolism).

Hydration. Adequate hydration (fluid loading) of the patient before and after administration of the contrast agent is essential. This is particularly important for patients with myeloma, diabetes mellitus, impaired renal function, as well as infants, young children, and elderly patients. Hemodynamic and electrolyte imbalances occur particularly easily in children under one year of age, especially newborns.

Cardiovascular diseases. Caution is advised when examining patients with severe cardiovascular diseases and pulmonary hypertension due to the risk of arrhythmias or hemodynamic disturbances. In rare cases, severe, life-threatening, or fatal cardiovascular events such as cardiac arrest, cardiopulmonary arrest, and myocardial infarction have occurred.

Central nervous system disorders.

Encephalopathy has been reported with iotrolan use (see section "Adverse reactions"). Contrast-induced encephalopathy may present with neurological dysfunction symptoms and signs such as headache, visual disturbances, cortical blindness, confusion, seizures, loss of coordination, hemiparesis, aphasia, unconsciousness, coma, and cerebral edema, occurring from several minutes to hours after iotrolan administration and usually resolving within several days.

The agent should be used with caution in patients with blood-brain barrier impairment, which may potentially increase contrast agent penetration and the risk of encephalopathy.

Patients with acute cerebral pathology, brain tumors, or a history of epilepsy are prone to seizures and require special attention. Increased risk of seizures and neurological reactions is observed in individuals with alcohol or drug dependence. Particular care should be taken during intravenous administration in patients with acute stroke or acute intracranial hemorrhage, as well as in those with blood-brain barrier damage, cerebral edema, or acute demyelinating processes.

In suspected contrast-induced encephalopathy, iotrolan administration should be discontinued and appropriate medical treatment initiated.

Renal disorders. The main risk factor for contrast-induced nephropathy is pre-existing renal dysfunction. Diabetes mellitus and the amount of iodine-containing contrast agent administered are factors influencing the development of renal impairment. Additional risk factors include dehydration, progressive atherosclerosis, low renal perfusion, and the presence of other nephrotoxic factors such as certain medications or surgical procedures.

Special precautions are required to prevent contrast-induced acute renal failure in patients with pre-existing renal impairment, diabetes mellitus, or those at risk. The same applies to patients with paraproteinemias (myeloma, Waldenström's macroglobulinemia).

Measures to prevent adverse reactions:

• Identification of patients at risk;
• Ensuring adequate hydration; if necessary, this may be achieved by continuous intravenous infusion initiated before contrast agent administration and continued until its renal excretion;
• Avoiding additional renal stress from nephrotoxic drugs, oral cholecystographic agents, renal artery compression, renal angioplasty, or surgical procedures—until the contrast agent is eliminated from the body;
• Minimizing the contrast dose;
• Repeated contrast examinations should be performed only after complete normalization of renal function following the last contrast agent administration.

Iodine-containing contrast agents may be administered to patients undergoing hemodialysis, as these agents are removed by hemodialysis.

Diabetic patients receiving metformin. Intravascular contrast studies with iodine-containing contrast agents may cause acute changes in renal function and may be associated with lactic acidosis in patients with renal impairment receiving metformin.

To prevent lactic acidosis in diabetic patients on metformin therapy, serum creatinine levels should be measured before intravascular administration of iodine-containing contrast agents.

1. Patients with normal serum creatinine levels or values greater than 60 mL/min/1.73 m² (CKD stages 1 and 2) may continue metformin as usual.
2. Patients with serum creatinine levels of 30–59 mL/min/1.73 m² (CKD stage 3):

a. Patients receiving intravenous contrast with normal serum creatinine or values greater than 45 mL/min/1.73 m² may continue metformin as usual.

b. Patients receiving intravascular or intravenous contrast with serum creatinine levels between 30 and 44 mL/min/1.73 m² should discontinue metformin at the time of contrast administration and not resume until 48 hours later or until renal function/serum creatinine returns to normal.

3. Metformin is contraindicated in patients with serum creatinine levels below 30 mL/min/1.73 m² (CKD stages 4 and 5) or with intercurrent illness causing hepatic impairment or hypoxia, and the use of iodine-containing contrast agents should be avoided.
4. In emergency situations where renal function is impaired or unknown, the physician must assess the risk-benefit ratio for the patient and take preventive measures: discontinue metformin, hydrate the patient, monitor renal function, and observe for symptoms of lactic acidosis. Metformin therapy should only be resumed if renal function/serum creatinine remains unchanged.

Renal and hepatic impairment. Extreme caution is required in patients with severe combined renal and hepatic dysfunction, as they exhibit significantly reduced contrast agent clearance. Patients undergoing hemodialysis may receive contrast agents for radiological procedures. There is no need to coordinate the timing between contrast agent injection and hemodialysis session, as there is no evidence that hemodialysis prevents contrast-induced nephropathy in patients with renal impairment.

Myasthenia gravis. Administration of iodine-containing radiographic contrast agents may exacerbate symptoms of myasthenia gravis.

Pheochromocytoma. In patients with pheochromocytoma undergoing invasive procedures, prophylactic α-blockers should be used to prevent hypertensive crises.

Thyroid dysfunction.

Patients with overt but undiagnosed hyperthyroidism, latent hyperthyroidism (e.g., nodular goiter), or functional autonomy of the thyroid gland (often elderly patients, particularly in iodine-deficient regions) are at increased risk of developing acute thyrotoxicosis after administration of iodine-containing contrast agents. The additional risk should be evaluated before administering iodine-containing contrast agents in such patients. Patients suspected of hyperthyroidism should be considered for thyroid function testing before contrast administration and/or prophylactic antithyroid therapy. Patients at risk should be monitored for signs of thyrotoxicosis for several weeks after iodine-containing contrast agent administration.

Thyroid function studies in adult and pediatric patients (including infants) after administration of iodine-containing contrast agents indicate a risk of hypothyroidism or transient suppression of thyroid function. Some patients required treatment for hypothyroidism.

Children.

Particular attention should be paid to children under 3 years of age, as impaired thyroid function at an early age may adversely affect motor skills, hearing, and cognitive development and may require temporary T4 replacement therapy. The incidence of hypothyroidism in patients under 3 years receiving iodine-containing contrast agents has been reported to range from 1.3% to 15%, depending on subject age and dose of contrast agent. Hypothyroidism is more frequently observed in newborns and preterm infants. Thyroid function should be evaluated in patients under 3 years of age after administration of iodine-containing contrast agents. If hypothyroidism is detected, appropriate treatment should be considered and thyroid function monitored until normalization.

Extravasation. Due to its isotonicity, Visipaque causes less local pain and swelling than hyperosmolar contrast agents. In case of extravasation, the injection site should be elevated and cooled. Surgical decompression may be necessary if compartment syndrome develops.

Visipaque may contain more than 23 mg of sodium per dose, depending on the indication. This should be considered for patients on a sodium-restricted diet.

Patient monitoring. After administration of the contrast agent, patients should be observed for at least 30 minutes, as most serious adverse reactions occur within this period. However, delayed hypersensitivity reactions may occur several hours or days after injection.

Intrathecal administration. After myelography, the patient should remain at rest for at least 1 hour in a supine position with the head and chest elevated by 20°. Afterwards, the patient may be mobilized, but bending should be avoided. If bed rest is required, the elevated head and chest position should be maintained for the first 6 hours. Patients with a suspected low seizure threshold should be monitored during this period. Outpatients should not be left unattended during the first 24 hours after the procedure.

Hysterosalpingography. Hysterosalpingography should not be performed during pregnancy or in cases of acute pelvic peritonitis.

Use during pregnancy or breastfeeding.

Pregnancy.

The safety of Visipaque during pregnancy has not been established. Preclinical experimental data on reproductive toxicity, embryofetal development, pregnancy course, and perinatal and postnatal development do not indicate direct or indirect harmful effects. Radiation exposure during pregnancy should be avoided if possible. The decision to perform radiographic examination with or without contrast agent should be carefully considered due to potential risks. The drug may be used during pregnancy only if absolutely necessary, according to physician recommendations and after careful benefit-risk assessment.

Newborns exposed to iodine-containing contrast agents during intrauterine development should have their thyroid function monitored.

Breastfeeding.

Contrast agents pass into breast milk in small amounts, and minimal absorption occurs in the infant's gastrointestinal tract. Breastfeeding may continue after administration of iodine-containing radiographic contrast agents.

Fertility.

The effect of Visipaque on human fertility has not been established. Preclinical animal studies do not indicate direct or indirect adverse effects on reproduction.

Ability to affect reaction speed when driving or operating machinery.

No studies on the effect of the drug on the ability to drive or operate machinery have been conducted. Driving and operating complex machinery are not recommended during the first 24 hours after intrathecal administration of contrast agents.

Method of administration and dosage.

For intraarterial, intravenous, intrathecal, and intracavitary administration.

If necessary, the preparation may be warmed to 37 °C (body temperature) prior to administration. The medicinal product may also be stored at 37 °C for up to 1 month prior to use (see section "Storage conditions").

The dose of the drug depends on the method of examination, age, body weight, cardiac output, the patient's general condition, and the technique of administration. Generally, the same concentration and volume of iodine should be used as with other commonly accepted iodine-containing radiographic contrast agents. Diagnostic data have been obtained with injected iopromide containing a lower concentration of iodine. Adequate hydration of the body is required before and after administration of the contrast agent, as with other radiographic contrast agents.

Doses indicated for intraarterial administration are intended for single injections, which may be repeated if necessary.

Recommended dosing regimen:

Intraarterial (i.a.) administration

Indications	Concentration	Volume
Arteriography Selective cerebral Aortography Peripheral Selective visceral intra-arterial CCA	270/320(1) mg iodine/ml; 270/320 mg iodine/ml; 270/320 mg iodine/ml; 270 mg iodine/ml;	5-10 ml/in. 40-60 ml/in. 30-60 ml/in. 10-40 ml/in.
Cardioangiography Adults Left ventricle and aortic root Selective coronary angiography Children	320 mg iodine/ml; 320 mg iodine/ml; 270/320 mg iodine/ml;	30-60 ml/in. 4-8 ml/in. depending on age, body weight and pathology (recommended max. total volume not more than 10 ml/kg)

Intravenous (IV) administration

Indications	Concentration	Volume
Urography Adults Children < 7 kg Children > 7 kg	270/320 mg iodine/ml; 270/320 mg iodine/ml; 270/320 mg iodine/ml;	40-80 ml(2) 2-4 ml/kg 2-3 ml/kg depending on age, body weight and pathology (max. 50 ml)
Phlebography	270 mg iodine/ml;	50-150 ml per limb
Contrast enhancement in CT Adults Head CT Body CT Children Head and body CT	270/320 mg iodine/ml; 270/320 mg iodine/ml; 270/320 mg iodine/ml;	50-150 ml 75-150 ml 2-3 ml/kg body weight up to 50 ml (in individual cases up to 150 ml may be administered)

Intrathecal administration

Indications	Concentration	Volume
Lumbar and thoracic myelography (lumbar administration) Cervical myelography (cervical or lumbar administration)	270 mg iodine/ml or 320 mg iodine/ml; 270 mg iodine/ml or 320 mg iodine/ml;	10-12 ml(3) 10 ml(3) 10-12 ml(3) 10 ml(3)

Intracavitary administration

The dose is individually adjusted for optimal visualization

Indications	Concentration	Volume
Arthrography	270 mg iodine/ml	1-15 ml
Hysterosalpingography (HSG)	270 mg iodine/ml	5-10 ml The recommended dose may be increased several times, e.g. in case of backflow into the vagina (doses up to 40 ml have been used)
Gastrointestinal tract examination Oral administration Adults Assessment of gastrointestinal transit Esophagus Stomach Children Rectal administration Children	320 mg iodine/ml; 320 mg iodine/ml; 320 mg iodine/ml; 270/320 mg iodine/ml; 270/320 mg iodine/ml;	Doses of 80-200 ml have been used Doses of 10-200 ml have been used Doses of 20-200 ml have been used 5 ml/kg body weight, doses of 10-240 ml have been used Doses of 30-400 ml have been used

(1) both concentrations can be used, but in most cases 270 mg iodine/mL is recommended;

(2) in individual cases, administration of higher doses is possible;

(3) to minimize the risk of adverse reactions, the total iodine dose should not exceed 3.2 g.

Elderly patients do not require dose adjustment.

Patients with hepatic and/or renal impairment do not require dose adjustment.

Children.

The drug can be used in children for performing coronary angiography, urography, contrast enhancement in computed tomography (CT), and gastrointestinal tract examinations. Recommended doses are provided in the section "Administration and dosage".

Overdose.

Overdose is unlikely in patients with normal renal function. Prolonged procedures involving high doses of the drug may affect renal function (elimination half-life – 2 hours). In case of accidental overdose, correction of fluid and electrolyte imbalance should be performed using infusion therapy. Renal function should be monitored for the following 3 days. If necessary, excess drug can be removed by hemodialysis. There is no specific antidote. Symptomatic treatment should be applied in case of overdose.

Side effects.

The following are possible adverse effects associated with radiological procedures involving the use of the drug Visipaque.

Adverse reactions related to the use of Visipaque are generally mild to moderate in clinical severity and reversible. Serious reactions and fatal outcomes occur only rarely. These may include: acute chronic renal failure, acute renal failure, anaphylactic or anaphylactoid shock, hypersensitivity reactions accompanied by cardiac events (acute coronary syndrome), cardiac arrest, cardiac and respiratory arrest, myocardial infarction.

Cardiac reactions may be caused by underlying disease or the procedure itself.

Hypersensitivity reactions may occur, usually manifesting as respiratory and skin reactions such as dyspnea, rash, erythema, urticaria, pruritus, serious skin reactions, angioedema, arterial hypotension, fever, laryngeal edema, bronchospasm, and pulmonary edema. In patients with autoimmune diseases, cases of vasculitis and signs of Stevens-Johnson syndrome have been observed. These reactions may develop immediately after administration or several days later. Hypersensitivity reactions may occur regardless of dose and route of administration. Mild symptoms may be the first signs of a severe anaphylactic reaction/shock.

Administration of the contrast agent should be stopped immediately, and if necessary, specific therapy should be initiated, including intravascular administration of medications. In patients receiving β-blockers, manifestations of hypersensitivity reactions may be atypical and may be mistaken for vagal reactions.

A minor transient increase in serum creatinine levels is a common occurrence after administration of iodinated contrast agents. This is usually not clinically significant.

Adverse effects are classified by frequency as follows:

Very common (≥ 1/10), common (≥ 1/100, <1/10), uncommon (≥ 1/1,000, <1/100), rare (≥1/10,000, <1/1,000), very rare (< 1/10,000), not known (frequency cannot be estimated from available data).

Adverse reactions associated with intravascular administration.

Blood and lymphatic system disorders.

Not known: thrombocytopenia.

Immune system disorders.

Uncommon: hypersensitivity reactions.

Not known: anaphylactic/anaphylactoid reactions, anaphylactic/anaphylactoid shock, including life-threatening or fatal anaphylaxis.

Endocrine disorders.

Not known: hyperthyroidism, hypothyroidism.

Psychiatric disorders.

Very rare: agitation, anxiety.

Not known: confusion.

Nervous system disorders.

Uncommon: headache.

Rare: dizziness, sensory disturbances including dysgeusia, paresthesia, parosmia.

Very rare: stroke, amnesia, syncope, transient tremor, hypoesthesia.

Not known: coma, disturbances in consciousness, seizures, transient contrast-induced encephalopathy*, caused by extravasation of contrast agents, which may present as sensory, motor, or general neurological dysfunction.

* Transient contrast-induced encephalopathy:

In rare cases, the contrast agent may cross the blood-brain barrier, leading to uptake of the contrast agent in the cerebral cortex, potentially causing contrast encephalopathy. Symptoms may include restlessness, transient cortical blindness, amnesia, hallucinations, paralysis, paresis, disorientation, transient speech disturbances, aphasia, dysarthria.

Eye disorders.

Very rare: cortical blindness (transient), visual disturbances including diplopia, blurred vision, eyelid edema.

Cardiac disorders.

Rare: arrhythmia (including bradycardia, tachycardia), myocardial infarction.

Very rare: cardiac arrest, palpitations.

Not known: heart failure, ventricular hypokinesia, coronary artery spasm, cardiac and respiratory arrest, conduction disorders, coronary thrombosis, angina pectoris.

Vascular disorders.

Uncommon: flushing.

Rare: arterial hypotension.

Very rare: arterial hypertension, ischemia.

Not known: shock, arterial spasm, thrombosis, thrombophlebitis.

Respiratory, thoracic and mediastinal disorders.

Rare: cough, sneezing.

Very rare: dyspnea, throat irritation, laryngeal edema.

Not known: non-cardiogenic pulmonary edema, respiratory arrest, respiratory failure, bronchospasm, throat obstruction, pharyngeal edema.

Gastrointestinal disorders.

Uncommon: nausea, vomiting.

Very rare: abdominal pain/discomfort, diarrhea.

Not known: acute pancreatitis, exacerbation of pancreatitis, salivary gland enlargement.

Skin and subcutaneous tissue disorders.

Uncommon: rash or toxicoderma, pruritus, urticaria.

Very rare: angioedema, erythema, hyperthyroidism.

Not known: bullous dermatitis, Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, acute generalized exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms (DRESS).

Musculoskeletal and connective tissue disorders.

Very rare: back pain, muscle spasms.
Not known: arthralgia.

Renal and urinary disorders.

Uncommon: acute renal failure or nephropathic toxicity (contrast-induced nephropathy).

Not known: increased blood creatinine levels.

General disorders and administration site conditions.
Uncommon: chest pain, sensation of altered body temperature.

Rare: hyperthermia, injection site reactions including extravasation, pain, and discomfort.

Very rare: asthenic condition (e.g., malaise, increased fatigue), facial swelling, localized edema.

Not known: edema.

Injury, poisoning and procedural complications.
Not known: iodism.

Adverse reactions associated with intrathecal administration.

Adverse reactions are delayed and may occur several hours or days after intrathecal administration. Their frequency approximately corresponds to the complication rate following lumbar punctures without contrast agent administration. When other non-ionic contrast agents are used, signs of meningeal irritation such as photophobia, meningism, and chemical meningitis may occur. Infectious meningitis should also be considered as a possible complication.

Immune system disorders.

Not known: hypersensitivity reactions, including anaphylactic/anaphylactoid reactions.

Nervous system disorders.
Uncommon: headache (may be severe and prolonged).

Not known: dizziness, transient contrast-induced encephalopathy (including hallucinations, amnesia, confusion, and other neurological symptoms).

Gastrointestinal disorders.
Uncommon: vomiting.

Rare: nausea.

Musculoskeletal and connective tissue disorders.

Not known: muscle spasms.

General disorders and administration site conditions.
Not known: tremor, injection site pain.

Adverse reactions associated with hysterosalpingography (HSG).

Immune system disorders.

Not known: hypersensitivity reactions.

Nervous system disorders.

Common: headache.

Gastrointestinal disorders.

Very common: abdominal pain.

Common: nausea.

Not known: vomiting.

Reproductive system disorders.

Very common: vaginal bleeding.

General disorders and administration site conditions.

Common: hyperthermia.

Not known: tremor, injection site reaction.

Adverse reactions associated with arthrography.

Immune system disorders.

Not known: hypersensitivity reactions, including anaphylactic/anaphylactoid reactions.

General disorders and administration site conditions.

Common: injection site pain.

Not known: tremor.

Adverse reactions associated with intracavitary administration.

Immune system disorders.

Not known: hypersensitivity reactions, including anaphylactic/anaphylactoid reactions.

Gastrointestinal disorders.

Common: diarrhea, abdominal pain, nausea.

Uncommon: vomiting.

General disorders and administration site conditions.

Not known: tremor.

Shelf life. 3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 30 °C.

Store in a place protected from secondary X-ray exposure.

Storage at 37 °C for up to 1 month prior to use is permitted.

Keep out of reach of children!

Incompatibilities.

There are no data on compatibility of the drug with other medicinal products; therefore, a separate syringe should be used for administration of Visipaque, and it should not be mixed with other medicinal products.

Packaging.

270 mg iodine/mL – 50 mL or 100 mL in a vial; 10 vials in a cardboard box.

320 mg iodine/mL – 20 mL, 50 mL, 100 mL, 200 mL, or 500 mL in a vial; 10 vials in a cardboard box.

Prescription category.

Prescription only.

Manufacturer.

GE Healthcare Ireland Limited, Ireland.

Manufacturer's address and place of business.

IDA Business Park, Carrigtohill, Co. Cork, Ireland.